DM 2

7. Explain the biochemical basis of hyperglycemia among patients with impaired glucose tolerance.

9. Interpret the FBS result of the patient.

The fasting test should be conducted on two separate occasions to ensure consistent results and in
order to avoid a false diagnosis.
This is the case as increased blood glucose levels may be as a result of Cushing’s syndrome liver or
kidney disease, eclampsia and pancreatitis.
Fasting test results:
Normal: 3.9 to 5.4 mmols/l (70 to 99 mg/dl)
Prediabetes or Impaired Glucose Tolerance: 5.5 to 6.9 mmol/l (100 to 125 mg/dl)
Diagnosis of diabetes: 7.0 mmol/l (126 mg/dl) or above

10. Discuss oral glucose tolerance test and its significance and describe how it is performed.

The most common glucose tolerance test is the oral glucose tolerance test (OGTT).
Before the test begins, a sample of blood will be taken.
You will then be asked to drink a liquid containing a certain amount of glucose (usually 75 grams). Your
blood will be taken again every 30 to 60 minutes after you drink the solution.
The test may take up to 3 hours.

Galactosemia

2. Discuss Galactose Metabolism. List the important compounds in our body in which Galactose is
needed for synthesis.

Galactose, which is metabolized from the milk sugar, lactose (a disaccharide of glucose and galactose),
enters glycolysis by its conversion to glucose-1-phosphate (G1P). This occurs through a series of steps
that is referred to as the Leloir pathway, named after Luis Federico Leloir who determined the overall
process of galactose utilization.
Galactose can exist in two different stereoisomeric forms; α-D-galactose and β-D-galactose. The α-form
is that which is metabolized in the Leloir pathway. Conversion of the β-form of galactose to the α-form
requires the enzyme galactose mutarotase encoded by the GALM gene (also known as aldose 1-
epimerase). The first reaction of the Leloir pathway is the phosphorylation of α-D-galactose by
galactokinase to yield galactose-1-phosphate. The galactokinase protein is encoded by the GALK1 gene
located on chromosome 17q25.1. The GALK1 gene spans 7.3 kbp and contains 8 exons that encode a
392 amino acid protein. There is another gene identified as GALK2 that was originally thought to be a
second galactokinse gene but was subsequently shown to be an N-acetylgalactosamine kinase.
Epimerization of galactose-1-phosphate to glucose-1-phosphate (G1P) requires the transfer of UDP from
UDP-glucose catalyzed by galactose-1-phosphate uridylyltransferase (GALT). The GALT gene is located
on chromosome 9p13.3 and is composed of 11 exons that generate two alternatively spliced mRNAs
that encode two distinct isoforms of the enzyme. GALT isoform 1 is a protein of 379 amino acids and
GALT isoform 2 is a protein of 270 amino acids. The GALT catalyzed reaction generates UDP-galactose
and G1P.
The UDP-galactose is epimerized to UDP-glucose by UDP-galactose-4 epimerase (GALE). The UDP
portion is exchanged for phosphate generating glucose-1-phosphate which then is converted to glucose-
6-phosphate (G6P) by phosphoglucose mutase. The GALE gene is located on chromosome 1p36.11 and
is composed of 13 exons that generate three alternatively spliced mRNAs all of which encode the same
348 amino acid protein. GALE catalyzes two distinct but analogous epimerization reactions, the
epimerization of UDP-galactose to UDP-glucose and the epimerization of UDP-N-acetylgalactosamine to
UDP-N-acetylglucosamine.
There are additional minor pathways of galactose metabolism in humans that do not involve all three of
the enzymes of the classical Leloir pathway. Galactose can be converted to UDP-glucose by the
sequential activities of GALK, UDP-glucose pyrophosphorylase 2 (UGP2), and GALE. Galactose can also
be reduced to galactitol by NADPH-dependent aldose reductase. This latter reaction becomes significant
in the context of GALT and GALK1 deficiencies that result in galactosemias (see below). Finally, galactose
can be oxidized to galactonate by galactose dehydrogenase. Under normal conditions, these alternative
pathways are responsible for the metabolism of only trace quantities of galactose.

Entry of galactose carbon atoms into the

glycolytic pathway.
Metabolism of galactose via the glycolytic
pathway requires a continuous supply of
UDP-glucose generated from glucose-1-
phosphate via the action of UDP-glucose
pyrophosphorylase 2 (encoded by the
UGP2 gene). The three enzymes that
convert galactose to glucose-6-phosphate
are encoded by the GALK, GALT, and
PGM1 genes. Humans express four
phosphoglucomutase (PGM) genes with
the PGM1 gene being expressed in most
tissues. The interconversion of UDP-
galactose and UDP-glucose requires the
enzyme encoded by the GALE gene.
6. Enumerate and explain the effects that will result if the condition is untreated.

 Can cause rapid, unexpected death due to an infection that invades the blood.
 May also develop brain damage
 Liver disease
 Cataracts
 Failure to gain weight or grow in length
 Poor feeding and poor suck
 Lethargy
 Irritability
 Low blood sugar, called hypoglycemia
 Seizures
 Enlarged liver that does not work properly
 Jaundice (yellow color to the skin or whites of the eyes)
 Bleeding
 Serious blood infections that could lead to shock and death
 Mild intellectual disabilities or learning delays
 Ataxia (unsteady gait)
 Delays in growth
 Speech problems and delays